Transient Receptor Potential Cation Channel, Subfamily A, Member 1 (TRPA1) protein has been characterized as a cold-activated channel with a lower activation temperature than the cold and menthol receptor, Transient Receptor Potential Cation Channel, Subfamily M, Member 8 (TRPM8) (Story, et al. (2003) Cell 112:819-829; McKemy ((2005) Molecular Pain 1:16). TRPA1 is a distant family member of TRP channels that shares little amino acid similarity with TRPM8. It is found in a subset of nociceptive sensory neurons where it can be coexpressed with the capsaicin/heat receptor, TRPV1, but not TRPM8. Consistent with the expression pattern of TRPA1, it has been identified on noxious cold-sensitive sensory neurons that also respond to capsaicin but not to menthol. It has also been demonstrated that mustard oil (allyl isothiocyanate) activates TRPA1 (Jordt, et al. (2004) Nature 427:260-265; Sawada, et al. (2007) Brain Research 1160:39-46). Moreover, the mouse TRPA1 channel is activated by pungent natural compounds present in cinnamon oil (cinnamaldehyde), wintergreen oil (methyl salicylate), clove oil (eugenol), and ginger (gingerol) (Bandell, et al. (2004) Neuron 41:849-857), wherein TRPA1 activation by cold temperature may convey a paradoxical burning pain sensation. In experiments in male Sprague-Dawley rats, it was demonstrated that pharmacologic blockade of TRPA1 by anti-nerve growth factor (NGF), p38 MAPK inhibitor, or TRPA1 antisense oligodeoxynucleotide in primary sensory neurons reversed cold hyperalgesia caused by inflammation and nerve injury (Obata, et al. (2005) J. Clin. Invest. 115: 2393-2401).
In this regard, compositions and methods associated with TRP and TRP-like channels are provided in U.S. Pat. No. 7,018,617 and U.S. Patent Application Nos. 20060142547 and 20050202539